Binap, (A+-)- → 2-(4-tert-Butylthiazol-2-ylamino)-6-(3-acetamidophenyl)pyrazine

HRID 16265

Reaktionsgleichung

Reaktionsgleichung von HRID 16265
[C:1]([NH:4][C:5]1[CH:6]=[C:7]([C:11]2[CH:16]=[N:15][CH:14]=[C:13](Cl)[N:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:3])[CH3:2].[C:18]([C:22]1[N:23]=[C:24]([NH2:27])[S:25][CH:26]=1)([CH3:21])([CH3:20])[CH3:19].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1>[C:18]([C:22]1[N:23]=[C:24]([NH:27][C:13]2[N:12]=[C:11]([C:7]3[CH:6]=[C:5]([NH:4][C:1](=[O:3])[CH3:2])[CH:10]=[CH:9][CH:8]=3)[CH:16]=[N:15][CH:14]=2)[S:25][CH:26]=1)([CH3:21])([CH3:20])[CH3:19]

Komponenten

6

Edukt 4

HCID 634876Binap, (A+-)-HCID 27342024-tert-Butyl-1,3-thiazol-2-amineHCID 116874302-(3-Acetamidophenyl)-6-chloropyrazineHCID 23676156Sodium t-butoxide

Produkt 1

HCID 114943702-(4-tert-Butylthiazol-2-ylamino)-6-(3-acetamidophenyl)pyrazineAusbeute 21 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel

Versuchsvorschrift

Following Method L, 2-(3-acetamidophenyl)-6-chloropyrazine (4a) (60 mg, 0.24 mmol), 4-(tert-butyl)-1,3-thiazol-2-amine (54.7 mg, 0.35 mmol), Pd(0)2 dba3 (9 mg, 0.01 mmol), BINAP (50 mg, 0.04 mmol), sodium tert-butoxide (33 mg, 0.34 mmol) and toluene (5 mL) were reacted at 85° C. for 16 hours. The same workup as is Method L produced a solid that was washed with 50 mL dichloromethane and filtered. The dichloromethane slowly evaporated to produce white crystals that were removed by filtration and washing with dichloromethane (10 mL). The dichloromethane was then evaporated and the resulting crude was chromatographed in silica gel using ethyl acetate: dichloromethane, 2:1, as eluent to furnish 18.5 mg of title compound. Yield: 21.0%. 1 H NMR (250 MHz, DMSO-d6) δ 1.30 (s, 9H), 2.10 (s, 3 H), 6.69 (s, 1 H), 7.47 (t, 1 H, 7.9 Hz), 7.69 (d, 1 H, 8.0 Hz), 7.89 (d, 1 H, 7.8 Hz), 8.38 (s, 1 H), 8.45 (bs, 1 H), 8.58 (s, 1 H), 10.11 (s, 1 H), 11.78 (bs, 1 H);

Aufarbeitung

  1. customwere reacted at 85° C. for 16 hours
  2. customproduced a solid
  3. washthat was washed with 50 mL dichloromethane
  4. filtrationfiltered
  5. customThe dichloromethane slowly evaporated
  6. customto produce white crystals that
  7. customwere removed by filtration
  8. washwashing with dichloromethane (10 mL)
  9. customThe dichloromethane was then evaporated
  10. customthe resulting crude was chromatographed in silica gel

Quellen und Nachweise

ORD-Eintrag
ord-6f12db6018d14117a4997409e78fe5d6
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07737152B2

Verknüpfte Notizen

Wird geladen…